The steroidal alkaloid tomatidine is an aglycone of α-tomatine, which is abundant in tomato leaves and has several biological activities. Tomatidine has been reported to inhibit the growth of cultured cancer cells in vitro, but its anti-cancer activity in vivo and inhibitory effect against gastric cancer cells remain unknown. We investigated the efficacy of tomatidine using human gastric cancer-derived 85As2 cells and its tumor-bearing mouse model and evaluated the effect of tomatidine-rich tomato leaf extract (TRTLE) obtained from tomato leaves. In the tumor-bearing mouse model, tumor growth was significantly inhibited by feeding a diet containing tomatidine and TRTLE for 3 weeks. Tomatidine and TRTLE also inhibited the proliferation of cultured 85As2 cells. Microarray data of gene expression analysis in mouse tumors revealed that the expression levels of mRNAs belonging to the type I interferon signaling pathway were altered in the mice fed the diet containing tomatidine and TRTLE. Moreover, the knockdown of one of the type I interferon-stimulated genes (ISGs), interferon α-inducible protein 27 (IFI27), inhibited the proliferation of cultured 85As2 cells. This study demonstrates that tomatidine and TRTLE inhibit the tumor growth in vivo and the proliferation of human gastric cancer-derived 85As2 cells in vitro, which could be due to the downregulation of ISG expression.

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Background/Objectives: Imidazole dipeptides (IDPs), carnosine and anserine, are endogenous antioxidants. The metabolism and functions of IDPs have mainly been investigated in rodents. However, the blood of primates, such as humans, contains carnosinase (CN1), which hydrolyzes IDPs. In non-primates, CN1 is absent, allowing IDPs to be distributed throughout tissues. There are concerns about whether the results of animal experiments can be directly applied to humans. Therefore, we aimed to investigate the blood change in the concentration and tissue distribution of IDPs following their oral administration to golden hamsters, the only non-primates known to possess CN1. Methods: Plasma CN1 activity was compared between hamsters and humans. Hamsters were administered IDPs (an anserine/carnosine mixture) purified from chicken meat at a dose of 1000 mg/kg. Blood samples were collected at time points up to 6 h after administration. Tissue samples were collected at 6 h after administration to measure the concentrations of IDPs and related substances. Additionally, IDP levels in human and mice tissues from previous studies were compared with that of hamster tissues in this study. Results: Hamster plasma CN1 activity was more than 10 times higher than that in humans. Although IDPs were not detected in IDP-treated hamster plasma, constituent amino acids of IDPs increased up to 1–2 h and Nπ-methyl-histidine (m-His) remained at high levels up to 6 h after administration. IDP levels in control tissues (vehicle) were similar to those in human tissues. In the IDP group, tissue IDPs were higher than those in the vehicle and m-His increased in all tissues. Conclusions: This study indicated that m-His levels increase in hamster tissues following a single oral administration of IDPs and strongly suggest that hamsters should be used in functional studies of IDPs in humans, focusing on the functionality of m-His.

Background/Objectives: Imidazole dipeptides (IDPs), carnosine and anserine, are endogenous antioxidants. The metabolism and functions of IDPs have mainly been investigated in rodents. However, the blood of primates, such as humans, contains carnosinase (CN1), which hydrolyzes IDPs. In non-primates, CN1 is absent, allowing IDPs to be distributed throughout tissues. There are concerns about whether the results of animal experiments can be directly applied to humans. Therefore, we aimed to investigate the blood kinetics and tissue distribution of IDPs following their oral administration to golden hamsters, the only non-primates known to possess CN1. Methods: Plasma CN1 activity was compared between hamsters and humans. Hamsters were administered IDPs (an anserine/carnosine mixture) purified from chicken meat at a dose of 1,000 mg/kg. Blood samples were collected at time points up to 6 h after administration. Tissue samples were collected at 6 h after administration to measure the concentrations of IDPs and related substances. Additionally, IDP levels in human and mice tissues from previous studies were compared with that of hamster tissues in this study. Results: Hamster plasma CN1 activity was more than 10 times higher than that in humans. Although IDPs were not detected in IDP-treated hamster plasma, constituent amino acids of IDPs increased up to 1–2 h and Nπ-methyl-histidine (m-His) remained at high levels up to 6 h after administration. IDP levels in control tissues (vehicle) were similar to those in human tissues. In the IDP group, tissue IDPs were higher than those in the vehicle and m-His increased in all tissues. Conclusions: This study suggests that IDPs and m-His levels increase in human tissues following a single oral administration of IDPs, and that m-His may serve as a substitute for IDPs.